APOL3 is a membrane-interacting protein with multifaceted roles in immunity and cellular homeostasis. Primary function: APOL3 controls membrane dynamics by regulating phosphatidylinositol-4-kinase-IIIB (PI4KB) activity, which governs membrane fission and fusion at the Golgi and mitochondria 1. Mechanism: APOL3 possesses detergent-like properties that dissolve bacterial and mitochondrial membranes by solubilizing lipids including cardiolipin and anionic phospholipids 23. Upon IFN-γ induction, APOL3 exhibits bactericidal activity against cytosolic pathogens and promotes ferroptosis in tumor cells through LDHA degradation, enhancing CD8+ T cell antitumor immunity 42. APOL3 additionally orchestrates mitophagy completion and facilitates mtDNA release from mitochondria following lysosomal damage, potentiating type I interferon responses 3. Disease relevance: Loss-of-function APOL3 variants (p.Q58*) increase chr22 kidney disease risk, particularly in APOL1 G1/G2 carriers, suggesting APOL3 protects against APOL1-induced renal injury 56. Clinical significance: APOL3 represents a novel immunotherapeutic target for overcoming ferroptosis resistance in colorectal cancer and offers potential for understanding APOL1-related kidney disease pathogenesis.