AMDHD1 (amidohydrolase domain containing 1) is a cytosolic hydrolase enzyme involved in the imidazolonepropionase activity and L-histidine catabolic pathway 1. Beyond its enzymatic function, AMDHD1 serves as a tumor suppressor in cholangiocarcinoma, where downregulation correlates with adverse clinicopathological features and poor prognosis 2. Mechanistically, AMDHD1 inhibits ubiquitination and degradation of SMAD4, enhancing TGF-β signaling to suppress cholangiocarcinoma cell proliferation and migration 2. AMDHD1 is also a recognized genetic determinant of circulating vitamin D levels, with genome-wide association studies identifying the rs10745742 variant as significantly associated with 25-hydroxyvitamin D concentrations 34. In nonalcoholic fatty liver disease, AMDHD1 expression is significantly decreased in nonalcoholic steatohepatitis patients compared to healthy controls, identifying it as a metabolic biomarker 5. Additionally, AMDHD1 expression is associated with pulmonary embolism risk through vitamin D metabolism pathways 6, and its expression is dynamically regulated during orthodontic compressive strain in periodontal ligament fibroblasts 7. During Xenopus metamorphosis, AMDHD1 is directly activated by thyroid hormone and expressed specifically in proliferating adult intestinal epithelial stem cells, suggesting a developmental role 1.