GPHA2 (glycoprotein hormone subunit alpha 2) functions as a heterodimeric glycoprotein hormone with GPHB5 that binds and activates the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production and playing a central role in controlling thyroid cell metabolism 1. This TSH receptor-activating complex, also known as corticotroph-derived glycoprotein hormone or thyrostimulin, exhibits unique binding characteristics with two distinct TSHR binding sites, distinguishing it from classical TSH 2. Beyond thyroid function, GPHA2 serves as a surface marker of limbal progenitor cells (LPCs) in the cornea, expressed in corneal limbal crypts and identified in approximately 0.41% of cultured limbal epithelial cells 3. GPHA2 expression is lost during ex vivo limbal epithelial cell expansion, indicating its association with progenitor cell identity 3. In the pituitary, GPHA2 is expressed in quiescent stem cells downstream of NOTCH2 signaling and activates TSHR signaling via pCREB induction 4. Clinically, GPHA2 represents a novel microbiota-derived metabolite target; oral indole-3-acetic acid supplementation upregulates hepatic GPHA2 expression, activating the TSH-THR-PGC-1α-PPARγ signaling cascade to suppress lipogenic genes and alleviate high-fat-diet-induced obesity 5. Additionally, GPHA2 has been identified as a prognostic gene in triple-negative breast cancer immunogenomics 6.