R3HDM1 (R3H domain containing 1) is an RNA-binding protein highly expressed in the human cerebral cortex 1 that plays a critical role in neuronal development. The protein functions primarily in dendritic growth and branching; knockdown of R3HDM1 in mouse embryonic hippocampal neurons suppressed these processes 1. Mechanistically, R3HDM1 antagonizes miR-128, which is encoded within intron 18 of R3HDM1 1. The protein recognizes uridine-rich sequences in 3'UTRs and acts as a positive post-transcriptional regulator by interacting with the translation initiation complex 2. R3HDM1 haploinsufficiency causes mild intellectual disability and developmental delay due to genetic imbalance between R3HDM1 and miR-128-1 1. The gene has also been identified as a gut microbiota-related key gene in nephrolithiasis pathogenesis 3 and as a crosstalk gene between chr2 obstructive pulmonary disease and periodontitis 4. Additionally, R3HDM1 variants are associated with elite strength athlete status in polygenic analyses 5. Clinically, R3HDM1 represents a therapeutic target for developmental neurological conditions and potentially for kidney stone disease and respiratory-periodontal pathophysiology.