PGGHG (protein-glucosylgalactosylhydroxylysine glucosidase) is a GH65 family enzyme that catalyzes the hydrolysis of glucose from disaccharide units (Glc-α1,2-Gal) linked to hydroxylysine residues in collagen and collagen-like proteins 1. The enzyme is encoded by the ATHL1 gene and contains three critical carboxyl residues (Asp301, Glu430, and Glu574) essential for catalytic activity 1. Structurally, PGGHG features a distinctive flat surface adjacent to its active site that facilitates collagen approximation and substrate recognition, enabling high specificity toward its glucosaccharide substrate 2. This specialized architecture is unique among GH65 family enzymes and supports selective recognition of glycosylated hydroxylysines 2. PGGHG functions within collagen glycosylation, a post-translational modification occurring in the endoplasmic reticulum that influences collagen secretion and fibril alignment 3. Beyond its primary metabolic role, PGGHG has emerged as having disease relevance. Genome-wide association studies implicate PGGHG in ectopic pregnancy pathogenesis, with altered PGGHG expression identified in fallopian tube epithelium networks associated with aberrant embryo implantation 4. Additionally, PGGHG DNA methylation patterns correlate with Crohn's disease status and severity, suggesting involvement in intestinal immune function and inflammation 5. These findings indicate PGGHG may represent a therapeutic target for collagen metabolism-related diseases and reproductive pathology.