GTF2IRD1 and Werner syndrome: cognitive impairment, mouse models, GTF2I, GTF2IRD1, CLIP2, LIMK1, NCF1, EIF4H, STX1A/B, FZD9, HIP1, CLDN3, FKBP6, organoid, induced pluripotent stem cell (iPSC) and forebrain organoids.<h4>Results</h4>Mouse models including multigene deletion strains recapitulating the WS critical region and single-gene knockout strains targeting Gtf2i, Gtf2ird1, Clip2 and Limk1 replicate key WS neurodevelopmental phenotypes, substantially contributing to mechanistic studies and therapeutic screening.