GCM2 (glial cells missing transcription factor 2) is a critical transcription factor essential for parathyroid gland development and function. GCM2 is expressed specifically in developing pharyngeal pouches and marks parathyroid-specific domains within the common thymus-parathyroid primordium before morphological distinctions are present 1. The protein functions by binding specific DNA sequences and activating gene transcription, including direct regulation of parathyroid hormone (PTH) expression through cooperation with other transcription factors like Gata3 and MafB 2. Single-cell analysis reveals GCM2 is highly expressed in parathyroid progenitor cells, with expression decreasing as cells mature into PTH-expressing epithelial cells 3. Loss-of-function GCM2 mutations cause familial isolated hypoparathyroidism, with affected individuals showing hypocalcemia and reduced PTH levels 4 5. Conversely, activating GCM2 variants are associated with familial isolated hyperparathyroidism and may contribute to more aggressive parathyroid disease, including parathyroid carcinoma 5 6. These variants show enhanced transcriptional activity and increased PTH promoter stimulation but have low penetrance in the general population 6. Understanding GCM2's role provides insight into parathyroid disorders and calcium homeostasis regulation 7.