IMPDH1 catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), representing the first committed and rate-limiting step in de novo guanine nucleotide synthesis 1. This enzyme plays a critical role in regulating cell growth through GTP biosynthesis and is subject to complex allosteric regulation and feedback inhibition by GTP 1. In retinal tissue, IMPDH1 exists as tissue-specific splice variants that assemble into micron-scale filaments, which enhance nucleotide production by desensitizing the enzyme to GTP inhibition 1. Phosphorylation at residue S477 in the dark acts as a mechanism to downregulate retinal GTP synthesis by modulating filament assembly 1. IMPDH1 enzymatic activity is further regulated through post-translational modifications, including SIRT5-mediated desuccinylation, which enhances activity and promotes tumor cell proliferation 2. Mutations in IMPDH1 cause autosomal dominant retinitis pigmentosa (RP10) and Leber congenital amaurosis 11, with early macular involvement typically appearing in the first decade of life 3. In cancer biology, IMPDH1-dependent purine biosynthesis represents a metabolic vulnerability in specific tumor subtypes, including ASCL1Low small cell lung cancer and high-risk head and neck squamous cell carcinoma 45. IMPDH inhibition effectively suppresses cancer cell proliferation and represents a potential therapeutic target in purine metabolism-dependent malignancies.