SYPL2 (synaptophysin like 2) is a tetratransmembrane transport vesicle protein with emerging roles in metabolism and disease. The protein is involved in communication between T-tubular and junctional sarcoplasmic reticulum membranes [UniProt], and GO annotations suggest functions in synaptic vesicle membrane organization and substantia nigra development. SYPL2 appears relevant to multiple disease processes. A low-frequency coding variant (rs62623713:A>G, p.E99G) in SYPL2 showed strong association with morbid obesity (beta=2.13, P=6.28×10⁻⁵), with mice lacking Sypl2 displaying reduced body weight 1. Additionally, SYPL2 expression is significantly downregulated in physically less active children, suggesting a role in cardiometabolic benefits and skeletal function 2. In kidney disease, a SYPL2 variant (rs12136063) associated with decreased estimated glomerular filtration rate in sickle cell disease patients 3. SYPL2 was identified as a potential biomarker for multiple psychiatric conditions, including non-atypical MDD and postpartum depression, though expression levels were characteristically low in brain tissue 4. Recent proteomics analysis identified SYPL2 (Sypl2) as one of eight shared differentially expressed targets across cancer cachexia models, suggesting involvement in severe cachexia pathology 5. Clinically, SYPL2 represents a novel candidate gene for understanding metabolic and systemic disease mechanisms, though its precise molecular function remains incompletely characterized.