GPHB5 (glycoprotein hormone subunit beta 5) functions as a heterodimeric glycoprotein hormone with GPHA2 that binds and activates the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production 1. The protein is expressed in corticotroph cells of the anterior pituitary, skin, retina, and testis 1. GPHB5 plays a central role in regulating metabolic homeostasis beyond classical thyroid function. In males, testosterone directly stimulates GPHB5 expression via androgen receptor signaling, and GPHB5 mediates testosterone's catabolic effects on adipose tissue by promoting white adipose tissue browning and energy expenditure; GPHB5 knockout in males causes severe obesity 2. In females, elevated circulating GPHB5 associates with insulin resistance and polycystic ovary syndrome, correlating positively with metabolic dysfunction markers (BMI, fasting glucose, triglycerides) and negatively with adiponectin 3. GPHB5 elevation also characterizes metabolic syndrome in women and responds to anti-diabetic interventions (metformin, GLP-1 agonists, thiazolidinediones) 4. Beyond metabolic regulation, GPHB5 has been identified as a potential biomarker in limbal epithelial stem cells 5 and rare variants associate with opioid dependence risk 6. These findings establish GPHB5 as a pleiotropic hormone linking sex hormone signaling to metabolic regulation and potentially relevant to neuropsychiatric conditions.