SYTL5 (synaptotagmin-like 5) is a RAB27A effector protein that functions in intracellular vesicle trafficking and mitochondrial homeostasis. Molecularly, SYTL5 directly interacts with the small GTPase RAB27A and localizes to mitochondria and vesicles containing mitochondrial material 1. The protein binds phospholipids and regulates mitophagy, the selective autophagic degradation of mitochondria, particularly under hypoxia 1. SYTL5 depletion reduces mitophagy, compromises mitochondrial respiration, and increases glucose uptake 1. Clinically, SYTL5 is significantly overexpressed in multiple cancers and promotes tumor progression through distinct mechanisms. In papillary thyroid carcinoma, SYTL5 enhances cell proliferation, migration, and invasion via NF-κB pathway activation 2. In thyroid carcinoma broadly, SYTL5 serves as a prognostic biomarker with high diagnostic accuracy (AUC 0.878) and is regulated by transcription factor ZNF384; SYTL5 knockdown promotes apoptosis and inhibits proliferation 3. In colorectal cancer liver metastasis, the SYTL5-overlapping lncRNA SYTL5-OT4 promotes vessel co-option and antiangiogenic therapy resistance by stabilizing ASCT2 4. Conversely, SYTL5 expression is reduced in adrenocortical carcinoma and correlates positively with patient survival 1. SYTL5 has also been implicated in multiple idiopathic cervical root resorption 5 and may serve as a biomarker for isothiazolinone-induced neurotoxicity 6.