DTWD2 is a tRNA-uridine aminocarboxypropyltransferase that catalyzes formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20a in the D-loop of cytoplasmic tRNAs, with weaker activity at position 20 1. This enzyme is essential for glycoRNA biosynthesis, wherein acp3U serves as an attachment site for N-glycans on tRNAs 2. Functionally, N-glycosylation of RNAs at acp3U prevents innate immune activation; genetic deletion of DTWD2 abrogates inflammatory responses to de-N-glycosylated RNAs and apoptotic cells by eliminating immunostimulatory acp3U exposure 3. Specifically, N-glycans on cell surface glycoRNAs conceal the hypermodified uracil base, blocking Toll-like receptor 3 and 7-dependent immune sensing and facilitating non-inflammatory clearance of dead cells 3. In mammals, double knockout of DTWD1 and DTWD2 causes growth retardation, indicating acp3U's physiological importance 1. Beyond immune function, DTWD2 variants associate with childhood body mass index and cognitive decline in language processing, particularly in APOE4 carriers 45. Additionally, DTWD2 copy number variations have been identified in primary open-angle glaucoma 6.