The gene is composed of 4 exons spanning a region of 9,520 base pairs.

The mRNA contains 1507 nucleotides. Alternative splicing has not been described. In prostate cancer cell lines RKIP transcription is repressed by Snail through an E-box in its promoter. Promoter methylation does not seem to cause loss of RKIP expression.

RKIP has two putative pseudogenes located on chromosomes 2 and 14. These are intronless sequences with no verified expression to date.

RKIP belongs to a highly conserved family of phospholipid-binding proteins, which have been recognized and studied for several years as PEBP. These proteins are represented in eukaryotes, bacteria, and archae. One of the interesting properties of some PEBP family members is that they are cleaved at the N-terminus to release an undecapeptide which has been named hippocampal cholinergic neurostimulating peptide (HCNP).

RKIP is an 187 amino acid protein with a molecular mass of 21-23 kDa. The crystal structures of human, bovine and plant PEBPs are solved revealing no homologies to domains of known functions. The structure of RKIP features a b-fold formed by two anti-parallel b-sheets, a small C-terminal aba element, and a cavity at the surface, which could accommodate a small anion such as a phosphoryl group (see diagram above). Amino acids forming this cavity are conserved among all PEBP family members and constitute the PEB motif.

RKIP and its mammalian homologs are widely expressed in tissues; it has been detected in lung, oviduct and ovary, mammary glands, uterus, prostate epithelium, thyroid, mesenteric lymph node, megakaryocytes of the heart; spleen, liver, and epididymis, testis, spermatids, Leydig cells, steroidogenic cells of the adrenal gland zona fasiculata, small intestine, plasma cells, and neural cells such as brain oliodendricytes, Schwann cells, and Pukinje cells.

RKIP is localized in the cytoplasm and at the plasma membrane.

RKIP inhibits the Raf/MEK/ERK cascade. Identified as a Raf-1 interacting protein in a yeast two-hybrid screen, RKIP was found to inhibit phosphorylation and activation of MEK by Raf-1. RKIP inhibits the phosphorylation of the N-region of Raf-1 by (21-activated kinase) Pak and Src family kinases thereby inhibiting activation of Raf-1. PKC phosphorylation of RKIP following GPCR stimulation causes its release from Raf-1. Classical and atypical PKCs can phosphorylate RKIP at serine 153 causing dissociation of the Raf-1 kinase domain and RKIP, indicating that PKC can mediate ERK activation through RKIP. Once free from Raf-1, RKIP was shown to bind GRK-2 and block its activity, promoting and enhancing G protein signaling and MEK/ERK signaling.
RKIP appears to support macrophage differentiation via inhibition of the NFKB pathway. RKIP inhibits the NF-kappaB pathway through interaction with NIK, TAK1, and IKK. RKIP was a novel effector of apoptosis signaling; this may occur by modulation of the NF-kappaB pathway and/or the regulation of the spindle checkpoint via Aurora B kinase and the spindle checkpoint by RKIP. RKIP regulation of Aurora kinase B and the spindle checkpoint through Raf-1/MEK/ERK signaling influences cell cycle fidelity.
RKIP has serine protease activity. Purified RKIP was found to inhibit the serine proteases thrombin, chymotrypsin, and neuropsin.
HCNP, the N-terminal fragment of RKIP, may play a role in phospholipid organization of the myelin sheath and septal cholinergic development of the hippocampus. HCNP can act on frog cardiac mechanical performance, exerting a negative inotropism. Results of these experiments suggest that RKIP/HCNP may be a new endocrine factor that regulates cardiac physiology. RKIP downregulation may be associated with the congenital heart disease manifested in Down syndrome. RKIP downregulation was found in the rat right ventricle and in the interventricular septum upon cardiac remodeling.
RKIP has been found in the male reproductive tract with implications in the organization of sperm membranes during spermiogenesis. It has been identified as a decapacitation factor in mouse spermatozoa. RKIP and other proteins inhibited progesterone-induced acrosome reaction and zona pellucida binding of sperm.

No significant sequence homology to other proteins. Humans have two known family members, RKIP and PEBP4. RKIP has high sequence identity to mouse, rat, bovine, and monkey phosphatidylethanolamine binding proteins.