MYORG (myogenesis regulating glycosidase) is an endoplasmic reticulum-localized enzyme that functions as an α-galactosidase with unusual specificity for Gal-α1,4-Glc structures, though its in vivo substrate remains unknown 1. The protein belongs to glycoside hydrolase family 31 and is primarily expressed in astrocytes 2. MYORG plays a critical role in brain phosphate homeostasis, with studies showing that it facilitates phosphate uptake by the transporter PiT2 in astrocytes, contributing to their high phosphate transport capacity 3. Biallelic mutations in MYORG cause autosomal recessive primary familial brain calcification (PFBC), also known as Fahr's disease, characterized by bilateral calcium-phosphate deposits in the basal ganglia and other brain regions 45. Patients with MYORG mutations typically exhibit extensive brain calcification with nearly 100% clinical penetrance, presenting with movement disorders, cognitive decline, and psychiatric disturbances 6. Disease-causing mutations result in loss of enzymatic activity and are distributed throughout the MYORG coding region 12. The pathogenic mechanism involves disruption of the neurovascular unit and phosphate dysregulation, contributing to blood-brain barrier dysfunction and progressive neurodegeneration 7.