KCTD13, potassium channel tetramerization domain containing 13, is a substrate-specific adapter for cullin3-based E3 ubiquitin ligase. It is involved in multiple biological pathways, including the regulation of cellular cytoskeleton, migration, proliferation, and neurodevelopment. Its function has been studied using various genetic models, especially mouse models [3,4].

In a TLE mouse model, the protein expression of KCTD13 dynamically changed during epileptogenesis. Knockdown of KCTD13 in the mouse hippocampus enhanced seizure susceptibility and severity, while overexpression had the opposite effect. KCTD13 facilitates lysine-48-linked polyubiquitination of GluN1, an N-methyl-D-aspartic acid receptor subunit, and its degradation through the ubiquitin-proteasome pathway, affecting glutamate synaptic transmission [1]. Kctd13-deficient mice display short-term memory impairment, with reduced density of mature spines in the hippocampus. Transcriptome analyses highlight dysregulation of pathways important in neurodevelopment, especially synaptic formation [2]. Also, Kctd13-knockout mice have penile and testicular anomalies like cryptorchidism and micropenis due to diminished androgen receptor function, with decreased levels of nuclear androgen receptor and SOX9 [3].

In conclusion, KCTD13 plays essential roles in neurodevelopment, synaptic transmission, and genitourinary tract development. Mouse models, especially KO and CKO mouse models, have been crucial in revealing its role in epilepsy, neurocognitive disorders, and genitourinary anomalies, providing potential therapeutic targets for these diseases.