ILKAP is a metal-dependent serine/threonine phosphatase belonging to the PP2C family 1 that regulates diverse cellular functions through reversible protein phosphorylation. As a focal adhesion protein, ILKAP selectively associates with integrin-linked kinase (ILK) to modulate cell adhesion and growth factor signaling, inhibiting the ILK-GSK3β axis and suppressing oncogenic transformation 2. ILKAP functions as a molecular switch controlling pro-survival and pro-apoptotic pathways: it activates apoptosis-signal-regulating kinase 1 (ASK1) while simultaneously inhibiting integrin-induced proliferation signals 2. In glioblastoma cells, ILKAP depletion sensitizes p53-wildtype tumors to radiotherapy by reducing DNA repair protein kinase (DNAPK) phosphorylation and increasing DNA damage accumulation 3. ILKAP also directly binds and dephosphorylates hypoxia-inducible factor 1α (HIF-1α), facilitating apoptosis under severe hypoxia 4. Conversely, in hepatocellular carcinoma, ILKAP promotes metastasis by dephosphorylating GSK3β and casein kinase 1, stabilizing β-catenin and activating WNT signaling 5. Clinical relevance includes associations with malignant melanoma susceptibility 6 and endometriosis pathogenesis, where reduced ILKAP expression correlates with disease severity 7. Palladin recruits cytoplasmic ILKAP to promote its pro-apoptotic function 8.