SYNJ2 (synaptojanin 2) is a phosphatidylinositol 5-phosphatase that dephosphorylates phosphoinositides including PIP2 and PIP3, functioning as a key enzyme in clathrin-mediated endocytosis and synaptic vesicle trafficking 1. The enzyme regulates phosphoinositide-dependent signaling pathways critical for membrane organization and receptor-mediated endocytosis 2. At the molecular level, SYNJ2 modulates the PI3K/AKT signaling pathway through dephosphorylation of PtdIns(3,4,5)P3 to PtdIns(3,4)P2, and interacts with signaling proteins including GRB2 to regulate cell proliferation and survival 3 4. SYNJ2 also functions in metabolic regulation by controlling PINK1 mRNA localization at mitochondria downstream of insulin signaling 5. Clinically, SYNJ2 dysregulation is associated with multiple malignancies. Elevated SYNJ2 expression predicts poor prognosis in lung squamous cell carcinoma (hazard ratio = 2.38) and correlates with invasive disease in breast cancer 6 3. In papillary thyroid carcinoma, high SYNJ2 expression promotes progression via angiogenesis and epithelial-mesenchymal transition pathways while predicting improved chemotherapy/immunotherapy response 7. SYNJ2 mutations impair auditory maintenance through mechanisms unrelated to synaptic exocytosis/endocytosis 1. Epigenetic dysregulation of SYNJ2 associates with anorexia nervosa and psychiatric comorbidity 8.