According to Entrez-Gene, human ILK maps to locus NC_000011.9. ILK gene contains 13 exons and spans 9.0 kb.

ILK encodes a predicted 451-amino acid protein with an apparent molecular mass of 59 kD based on SDS-PAGE. Northern blot analysis showed that the 1.8-kb ILK mRNA is widely expressed.

An ILK pseudogene has been found in mice, predicted gene 6263 (Gm6263).

ILK is a widely expressed modular protein composed of three major domains: an N-terminal domain that contains four ankyrin repeats, a central pleckstrin homology (PH)-like domain and a C-terminal kinase domain. The N-terminal ankyrin domain binds to PINCH (particularly interesting new cysteinehistidine protein) - an adaptor protein that complexes with ILK in the cytoplasm prior to active recruitment of ILK to focal adhesion sites - and to ILK-associated protein (ILKAP) - a protein phosphatase 2C (PP2C)-family protein phosphatase that negatively regulates ILK signaling (McDonald et al., 2008a). Adjacent to the ankyrin repeats, a sequence motif present in PH domains binds to the second messenger PI(3,4,5)P3 and a PI3-kinase-dependent kinase activation has been reported (Delcommenne et al., 1998; Boulter and Van Obberghen-Schilling, 2006). The C-terminus kinase domain also interacts with integrins, as well as with the focal adhesion proteins paxillin (Nikolopoulos and Turner, 2001; Nikolopoulos and Turner, 2002) and parvins (Hannigan et al., 2005; Legate et al., 2006), which link ILK, and therefore integrins, to the actin cytoskeleton.

ILK is ubiquitously expressed in most tissues, with predominance at skeletal muscle, heart, kidney and pancreas. Increased expression of ILK is correlated with progression of several tumor types, constituting an attractive therapeutic target in human cancer.

ILK is generally considered a cytosolic protein localized at focal adhesions, however ILK co-localizes with tubulins and many centrosomal and mitotic spindle associated proteins at centrosomes.

Integrin-linked kinase (ILK) (Hannigan et al., 1996) is a multifunctional protein kinase which is implicated in a large number of cellular processes and diseases, participating in signal transduction pathways that control cell survival, differentiation, proliferation and gene expression in mammalian cells (Wu, 2001). ILK, PINCH1 and α-parvin form a ternary complex termed IPP (ILK-PINCH-parvin) that localizes to both focal adhesions (FAs) and fibrillar adhesions (FBs) and is essential for several integrin-dependent functions. The IPP complex, interacts with the cytoplasmic tail of β integrins, resulting in the engagement and organization of the cytoskeleton as well as activation of signalling pathways. Deletion of the genes encoding ILK or PINCH1 similarly blocks maturation of FAs and FBs by downregulating expression or recruitment of tensin and destabilizing α5β1-integrin-cytoskeleton linkages (Legate et al., 2006; Stanchi et al., 2009; Elad et al., 2013). The kinase activity of ILK is stimulated by integrins and soluble mediators, including growth factors and chemokines, and is regulated in a phosphoinositide 3-kinase (PI3K)-dependent manner. The activity of ILK is antagonized by phosphatases such as ILKAP and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) (McDonald et al., 2008a). Important downstream targets of ILK signaling include PKB/Akt, GSK-3, β-catenin, p44/p42 MAP kinases, the myosin light chain (MLC) (Hannigan et al., 2011) and the Hippo pathway through Merlins phosphatase MYPT1 (Serrano et al., 2013c). AKT is a regulator of cell survival and apoptosis. To become fully activated, PKB/Akt requires phosphorylation at two sites, threonine 308 and serine 473. Phosphorylation at serine 473 depends on PI3K activity (Persad et al., 2001), the rictor-mTOR complex (Sarbassov et al., 2005) and the ILK-Rictor complex (McDonald et al., 2008b). GSK-3 is phosphorylated and inactivated at serine 9 by ILK, regulating the cell cycle through proteolysis of cyclin D1 and activation of the transcription factor AP1 (Troussard et al., 1999). Inactivation of GSK-3 stabilizes β-catenin, whose accumulation is related to deregulation of proliferation, migration and differentiation (Oloumi et al., 2004). ILK can directly phosphorylate MLC on Ser18/thr19 influencing in cell contraction, motility and migration (Deng et al., 2001). ILK function is required in TGFβ-1-induced EMT in mammary epithelial cells, and the ILK/Rictor complex has been identified as a potential molecular target for preventing/reversing EMT (Serrano et al., 2013b). But ILK can also directly regulate EMT by promoting the expression of Snail transcriptionally (McPhee et al., 2008) and via posttranslational modification through GSK-3b.
ILK also localize to centrosomes, where it is recruited by RUVBI1/2, and it regulates mitotic spindle assembly by promoting Aurora A kinase/TACC3/ch-TOG interactions (Fielding et al., 2008) as well as centrosome clustering through the microtubule regulating proteins TACC3 and ch-TOG (Fielding et al., 2011). In addition, ILK regulates microtubule dynamics since overexpression of ILK in HeLa cells is associated with a shorter duration of mitosis and decreased sensitivity to paclitaxel, a chemotherapeutic agent that suppresses microtubule dynamics and conversely, the use of a small molecule inhibitor selective against ILK, QLT-0267, results in suppressed microtubule dynamics (Lim et al., 2013). ILK regulation of microtubules is critical for proper trafficking of caveolin-1-containing vesicles. ILK controls this process by regulating microtubule stability through the recruitment of the scaffold protein IQGAP1 and its downstream effector mDia1 to nascent, cortical adhesion sites. In the absence of ILK, caveolae remain associated with dynamic microtubules, fail to stably fuse with the plasma membrane, and subsequently accumulate in intracellular structures (Wickström et al., 2010).

The ILK gene is highly conserved in a total of 24 species. The most representatives are human, mouse, chicken, lizard, African clawed frog, zebrafish, fruit fly, worm.

1. ILK mutation causes human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells (Knoll et al., 2007).
2. Embryonic lethality was observed in Xenopus laevis (Yasunaga et al., 2005) and mouse (Sakai et al., 2003) models of ILK ablation, and this was attributed to defects in adhesive and migratory mechanics.