TSHB encodes the beta subunit of thyroid-stimulating hormone (TSH), a critical component of the hypothalamic-pituitary-thyroid axis that controls thyroid structure and metabolism 1. As a hormone with G protein-coupled receptor signaling activity, TSH is synthesized in anterior pituitary thyrotroph cells and regulated by thyrotropin-releasing hormone (TRH) through transcription factors including Pit-1/GHF-1, with fine-tuning by thyroid hormone negative feedback at its promoter 2. Beyond classical endocrine functions, TSHB is expressed in adipose tissue where it acts as a paracrine factor modulating cholesterol metabolism 3. Mutations in TSHB cause central congenital hypothyroidism, characterized by low thyroxine with low or normal TSH levels, evading standard neonatal TSH-based screening 41. This condition affects approximately 1 in 16,000 neonates and requires early detection to prevent mental retardation 1. Population studies indicate TSHB variants are relatively rare (carrier frequency 0.04%), contributing minimally to overall congenital hypothyroidism prevalence compared to dyshormonogenesis genes 5. Notably, TSHB expression requires intact pituitary architecture and cellular organization, as dispersed cultured cells lose basal and TRH-responsive TSHB expression 6.