The gene encompasses 6.509 kb of gDNA.

Five variant mRNA transcripts have been identified. These include transcripts using different 5 untranslated regions (UTRs) including exon 1 deletions, and transcripts using different 3UTR regions. Using rapid amplification of cDNA ends (RACE) different KLK7 5UTR sequences were identified from RNA extracted from pancreas, skin and ovarian cells, suggesting the expression of tissue specific KLK7 transcripts.

Not identified.

Full-length KLK7 (253 amino acids) has a secretion signal (pre-) peptide (22 amino acids), followed by an activation (pro-) peptide (7 amino acids) and the mature chain (224 amino acids) with 1 potential N-linked glycosylation site. The catalytic triad of His70, Asp112 and Ser205 (relative to ATG1) is conserved and is essential for proteolytic activity. After synthesis as a KLK7 full-length protein, the signal peptide is then cleaved and pro-KLK7 (zymogen) is subsequently secreted from the cell. On activation, the propeptide is removed and the zymogen becomes the mature active enzyme. KLK7 can complex with antileukoprotease (secretory leukocyte protease inhibitor), elafin, Lympho-epithelial Kazal type inhibitor (LEKTI) fragments, and a member of a2-macroglobulin (a2M) protease inhibitor family, a2-macroglobulin-like 1 (a2ML1).
X-ray structures of recombinant full-length KLK7 from E. coli and insect cells have been solved, from which the most distinguishing features of KLK7 are the short 70-80 loop and the unique S1 pocket, which prefers P1 Tyr residues. KLK7 displays a unique chymotrypsin-like specificity for Tyr, which is preferred at P2. In addition, KLK7 exhibits large positively charged surface patches, representing putative exosites for prime side substrate recognition.
Similar to several other KLKs and based on the binding of metal to histidine such as His99, the KLK7 activity is inhibited by Zn⁺⁺ and Cu⁺⁺ at low micromolar concentrations. KLK7 induced degradation of corneodesmosin and desmocollin 1 with similar efficiency in acidic (pH 5.6) and neutral (pH 7.2) conditions. KLK7 activity is modulated by water content in stratum corneum as KLK7 activity increased significantly in an environment of high relative humidity. KLK7 also demonstrated a tolerance to water restriction suggesting that it may be adapted to function in the water-restricted stratum corneum. Thus, relative humidity modulates desquamation by its effect upon KLK7 activity, possibly other desquamatory hydrolases and adapted KLK7 function in water-deplete skin.
An N-terminal truncated KLK7 isoform (181 amino acids) initiating from the putative ATG2 would not have the pre-pro-region and 43 amino acids from the N-terminus of full-length KLK7. The histidine which is part of the catalytic triad is also omitted which would result in a proteolytic inactive protein. The presence of this isoform has not yet been confirmed in human tissues or biological fluids.

Full-length KLK7 protein was originally purified in human skin and named stratum corneum chymotryptic enzyme (SCCE, hSCCE). KLK7 cDNA was originally isolated from a keratinocyte derived library and designated PRSS6. Although Northern blot analyses have shown that KLK7 mRNA is predominantly localised to skin and pancreas, more sensitive RT-PCR experiments have shown that brain, kidney, ovary, bone, breast, endometrium, spinal cord, lung, prostate tissue and salivary tissue express KLK7 mRNA at low to modest levels. High KLK7 mRNA has been detected in malignancies of ovary, breast, lung and brain.
KLK7 protein has been detected by ELISA in a wide range of tissues at low (adrenal, bladder, cervix, fallopian tube, kidney, lung, lymph node, muscle, ovary, salivary gland, small intestine, spinal cord, spleen, thyroid gland, tonsil, trachea and vagina) to high (oesophagus, heart, liver and skin) levels. Modest levels of KLK7 protein have also been detected in human body fluid, such as, seminal plasma, breast milk, ovarian cancer ascites, salivary and cervicovaginal fluid.
In normal skin, KLK7 is expressed in late epidermal differentiation and found at all sites of epithelial cornification. Consequently, KLK7 is used as a marker for terminal epidermal differentiation. In normal epidermis, KLK7 was detected in a population of dendritic cells and in high suprabasal keratinocytes. KLK7 was also found in reconstructed human epidermis and its expression was suppressed by retinoic acid. An increased expression of KLK7 was found in suprabasal cells in orthokeratotic and parakeratotic areas of the lesions of oral lichen planus (an inflammatory disease) and benign oral keratosis (a non-inflammatory disease).
High KLK7 protein levels have been detected in the tissues of lung, breast, ovarian and squamous cervical cancers, oral squamous cell carcinoma and cervical adenocarcinoma tissues from patients. However, KLK7 is down regulated in cancerous prostate tissues compared to normal prostate tissues. KLK7, along with KLK6 and KLK10, is decreased in cerebrospinal fluid of frontotemporal dementia patients.

Full-length KLK7 is localised intracellularly in the cytoplasm prior to secretion. KLK7 protein is co-localised with KLK5 in skin and acinar cells of the pancreas by immunohistochemical staining.
The putative N-terminal truncated KLK7-181 isoform is potentially not secreted as it does not have a signal peptide, and cellular localisation remains to be determined.

To date, the major biological functions of KLK7 are associated with the skin and related epithelial tissues, such as hair follicles, oral mucosa and glandular lobules. KLK7 is involved in keratinization, stratum corneum formation, and turnover/desquamation of the skin through the degradation of cell adhesion glycoproteins, such as corneodesmosin, desmocollin 1 and plakoglobin. KLK7 has also been shown to cleave insulin B chain, degrade fibronectin, fibrinogen and interleukin 1beta (IL-1b), as well as activate pro-IL-1b. KLK7 and KLK5 can control activation of the human cathelicidin precursor protein, hCAP18, implying their ability to control innate immune defence.
An in vitro study showed that UVB radiation can increase KLK7 and KLK5 expression at both mRNA and protein levels in keratinocyte (HaCat) cells. In the epidermis, the major inhibitor of KLK7, antileukoprotease (secretory leukocyte protease inhibitor) is produced by keratinocytes and can inhibit detachment of corneocytes from human plantar callus in vitro, while a weaker KLK7 inhibitor, elafin (skin-derived antileukoprotease), can reduce the shedding of corneocytes. Established epidermal mouse models overexpressing KLK7 have been shown to develop chronic itchy dermatitis. Further characterisation of these models also revealed epidermal hyperproliferation, decreased skin barrier function, and decreased expression of MHC II antigen in keratinocytes. These data provide an in vivo pathophysiological foundation that KLK7 plays an important role in skin, such as listed those below.
KLK cascade activation systems have been described. KLK7 is activated by KLK5 and KLK12. KLK7 activates other members of the kallikrein-related peptidase family including KLK1, KLK2, prostate specific antigen (PSA/KLK3) and KLK9.
The function of the putative N-terminal truncated KLK7 remains to be established.

At the protein level, KLK7 shares 28% (KLK12), 33% (KLK9), 36% (KLK10, 11), 37% (KLK1, KLK3/PSA), 38% (KLK2, KLK5, KLK6, KLK13), 40% (KLK8), 41% (KLK14), 43% (KLK4) and 42.6% (KLK15) sequence homology with other members of the kallikrein-related peptidase family.

An AACC insertion in the 3UTR of the KLK7 gene has been found, which altered the common allele AACC to the rare allele AACCAACC. This insertion was found to be associated with atopic dermatitis.