GPHA2 (glycoprotein hormone subunit alpha 2) is a secreted glycoprotein that functions as the common alpha subunit of thyrostimulin, a heterodimeric hormone formed with GPHB5. This heterodimer activates the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production and control of thyroid cell metabolism 1. The GPHA2/GPHB5 complex exhibits unique TSHR binding properties distinct from canonical TSH, with evidence of two binding sites on the receptor 2. Beyond its canonical endocrine role, GPHA2 functions in tissue homeostasis. In the cornea, GPHA2 serves as a surface marker for limbal progenitor cells (LPCs) and is downregulated during ex vivo expansion 3. In the pituitary, GPHA2 is expressed in quiescent stem cells downstream of NOTCH2 signaling and activates TSHR-mediated signaling that may impact pituitary development 4. Recent mechanistic studies reveal GPHA2 participates in metabolic regulation independent of systemic thyroid hormone. Oral indole-3-acetic acid supplementation upregulates hepatic Gpha2 expression in high-fat-diet-induced obese mice, activating TSH-receptor-mediated signaling that suppresses lipogenic genes and improves metabolic homeostasis 5. GPHA2 has been identified as a prognostic gene in triple-negative breast cancer based on immune microenvironment analyses 6. The gene's diverse tissue expression suggests pleiotropic functions beyond thyroid regulation.