biostudies-literatureUnknownSong RNIDDK NIH HHSNHLBI NIH HHSNIGMS NIH HHSMaintaining intestinal homeostasis relies on the intricate interplay among the mucosal epithelium, immune system, and host microbiome. A key question is how innate immune cells sense and process microbes in the gut lumen, eliciting appropriate protective responses without causing tissue injury. Clearance of invading microbes and initiation of downstream inflammatory responses are central to this process and require proper function of the endolysosomal system. Dysfunction of this system can predispose the host to chronic inflammatory disorders and acute infections. Here, through forward genetic screening of N-ethyl-N-nitrosourea (ENU)-mutagenized mice and CRISPR/Cas9 validation, we identify <i>Lrmda</i>, encoding leucine-rich melanocyte differentiation-associated protein (LRMDA), as a key rbioRxiv : the preprint server for biology2025.07.16.665158https://www.ebi.ac.uk/biostudies/studies/S-EPMC12338710biostudies-literatureThe Rab32-LRMDA-Retriever Complex is a Key Regulator of Intestinal Immune Homeostasis.PMC12338710R01 DK107733R01 DK133229R35 GM128786R01 HL179813R01 DK119360Turer EESingla ALiu QDiwaker AChen BKramer DABeutler BBurstein ESong RMoresco JJNgoka CBoesch DJReinecker HCfalseThe Rab32-LRMDA-Retriever Complex is a Key Regulator of Intestinal Immune Homeostasis.Maintaining intestinal homeostasis relies on the intricate interplay among the mucosal epithelium, immune system, and host microbiome. A key question is how innate immune cells sense and process microbes in the gut lumen, eliciting appropriate protective responses without causing tissue injury. Clearance of invading microbes and initiation of downstream inflammatory responses are central to this process and require proper function of the endolysosomal system. Dysfunction of this system can predispose the host to chronic inflammatory disorders and acute infections. Here, through forward genetic screening of N-ethyl-N-nitrosourea (ENU)-mutagenized mice and CRISPR/Cas9 validation, we identify <i>Lrmda</i>, encoding leucine-rich melanocyte differentiation-associated protein (LRMDA), as a key r2025-01-01T00:00:00Z2025 Jul2026-04-08T15:51:00.35Z2026-04-08T05:38:11.234ZS-EPMC123387104079143210.1101/2025.07.16.665158