GTPase IMAP family member 5 (GIMAP5)

GTPase IMAP family member 5 (GIMAP5) is a small GTPase enzyme belonging to the immunity-associated nucleotide-binding protein family, encoded by the human GIMAP5 gene located on chromosome 7q36.1. It is predominantly expressed in lymphocytes and is essential for T cell survival, lymphocyte homeostasis, and immune tolerance. GIMAP5 functions as an antiapoptotic protein, regulating key intracellular signaling pathways such as the inactivation of glycogen synthase kinase-3β (GSK3β) following T cell receptor stimulation. Dysfunction or loss-of-function mutations in GIMAP5 can lead to lymphopenia, impaired T cell proliferation, autoimmunity (such as type 1 diabetes and systemic lupus erythematosus), allergic diseases (asthma), and colitis. In cancer, particularly hepatocellular carcinoma, GIMAP5 is downregulated and may serve as a disease biomarker. Therapeutically, the GIMAP5-GSK3β axis is targetable with GSK3 inhibitors, which have shown potential in preclinical models for correcting immune dysregulation associated with GIMAP5 deficiency. Overall, GIMAP5 is a multifaceted regulator of immune cell integrity, apoptosis, and stress responses, with key diagnostic and therapeutic implications across immune and inflammatory diseases.

Other names

IAN4L1IAN5IMAP3IAN-5hIAN5HIMAP3IRODNCPH2Immunity-associated nucleotide 4-like 1 proteinImmunity-associated nucleotide 5 proteinImmune-associated nucleotide-binding protein 5Immunity-associated protein 3Inhibitor of radiation- and OA-induced apoptosis

GSK3 inhibition restores T cell survival/function in GIMAP5 deficiency by correcting excessive DNA damage, normalizing c-Myc and NFATc1 signaling, and rescuing proliferation