Defective recognition of a nonclassical nuclear localization signal in neurodevelopmental disorders

In this issue of Structure, Gonzalez et al. present the cryo-EM structure of Karyopherin-β2 bound to the proline-tyrosine nuclear localization signal (PY-NLS) of heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2). The structure advances our understanding of not only the diversity of PY-NLSs but also the pathogenic mechanisms arising from HNRNPH2 variants. In this issue of Structure, Gonzalez et al. present the cryo-EM structure of Karyopherin-β2 bound to the proline-tyrosine nuclear localization signal (PY-NLS) of heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2). The structure advances our understanding of not only the diversity of PY-NLSs but also the pathogenic mechanisms arising from HNRNPH2 variants.