Pkd2l1, also known as TRPP2 or TRPP3, is a member of the transient receptor potential family and forms ciliary ion channels [1,3,5,8,9,10]. It is involved in multiple biological processes. In neurons, it may be related to brain electrical signaling and in spinal cord, it is associated with sensory functions of cerebrospinal fluid-contacting neurons (CSF-cNs) [1,2]. It also participates in processes like hedgehog signaling, intestinal development, and sour tasting [8]. Genetic models, especially mouse models, have been crucial in studying its functions.

Loss of Pkd2l1 expression in mice leads to ablation of primary ciliary maturation and attenuation of neuronal high-frequency excitability in hippocampal neurons, resulting in seizure susceptibility and autism spectrum disorder-like behavior, suggesting it is a regulator of hippocampal excitability [1]. In zebrafish, loss of Pkd2l1 nearly abolishes CSF-cN calcium activity and single channel opening, and adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, indicating its role in mechanoception in CSF-cNs and maintenance of spine curvature [4]. In mouse spinal cords, Pkd2l1+ CSF-cNs have neural stem cell properties both in vitro and in vivo, and their activation and proliferation can be induced by spinal cord injury, suggesting a potential role in spinal cord injury recovery [6,7].

In conclusion, Pkd2l1 plays essential roles in neuronal excitability regulation, mechanoception in CSF-cNs, and maintenance of spine curvature. The study of Pkd2l1 knockout mouse models has provided valuable insights into its functions and its potential involvement in neurological and spinal-related diseases, such as autism-like behaviors and spine curvature disorders.