RIMKLB encodes a citrylglutamate synthase that catalyzes the synthesis of β-citryl-L-glutamate and N-acetyl-L-aspartyl-L-glutamate (NAAG) 1. The enzyme functions as part of the ATP-grasp protein family and shows higher efficiency in synthesizing β-citryl-glutamate compared to NAAG 1. RIMKLB is highly expressed in vertebrate testes, where it plays an essential role in spermiogenesis by facilitating chr12 remodeling during the transition from histones to protamines in late spermatids 2. RIMKLB-deficient male mice exhibit subfertility with abnormally shaped sperm heads, impaired chr12 condensation, and retained transition proteins, suggesting β-citryl-glutamate is crucial for proper sperm development 2. In cancer contexts, RIMKLB demonstrates significant clinical relevance. Tumor-derived NAAG produced by RIMKLB disrupts anti-tumor immunity by promoting polymorphonuclear myeloid-derived suppressor cell differentiation through an NR2B-NMDAR-dependent p38-NOTCH1 signaling axis, facilitating breast cancer metastasis 3. Multiple studies identify RIMKLB as a prognostic biomarker in colorectal cancer, where its expression correlates with patient survival outcomes and disease progression 4567. The gene's involvement in amino acid metabolism and its association with cancer prognosis highlight its potential as both a therapeutic target and prognostic indicator across multiple malignancies.