Novel CDKL5 enzyme variants are provided, as well as fusion proteins comprising full-length CDKL5 polypeptides or CDKL5 variants. Such fusion proteins can include cell-penetrating polypeptides and optionally comprising a leader signal polypeptide and/or tags. Also provided are methods of producing such CDKL5 variants and fusion proteins, as well as pharmaceutical compositions, methods of treatment, and uses of such recombinant proteins.提供了新穎的CDKL5酶變體、以及包含全長CDKL5多肽或CDKL5變體的融合蛋白。此類融合蛋白可以包括細胞穿透多肽和視需要包含前導訊號多肽和/或標籤。還提供了產生此類CDKL5變體和融合蛋白之方法、以及此類重組蛋白的藥物組成物、治療方法和用途。