G6PC3 encodes glucose-6-phosphatase catalytic subunit 3, a ubiquitously expressed endoplasmic reticulum enzyme that hydrolyzes glucose-6-phosphate to glucose, functioning in gluconeogenesis and glycogenolysis 1. The enzyme likely operates as part of a complex with the glucose-6-phosphate transporter SLC37A4 to facilitate glucose production 2. Bi-allelic G6PC3 mutations cause severe congenital neutropenia type 4 (SCN4), a multi-system autosomal recessive disorder 1. Neutropenia results from defective metabolite repair leading to intracellular accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), which inhibits glycolysis in neutrophils and triggers increased apoptosis 34. Loss-of-function mutations reduce enzyme activity and induce endoplasmic reticulum stress 1. G6PC3 deficiency presents with severe congenital neutropenia, recurrent bacterial infections, thrombocytopenia, cardiac defects, and urogenital anomalies, with phenotypic heterogeneity including inflammatory bowel disease and growth retardation 15. SGLT2 inhibitors (empagliflozin, dapagliflozin) enhance urinary 1,5-AG excretion, reducing toxic metabolite accumulation and improving neutropenia and infections in pediatric patients 6. G-CSF treatment improves neutrophil numbers and prevents infections 1, while lentiviral gene therapy and vitamin B3 supplementation restore granulopoiesis in patient-derived iPSCs 7.