Kif19a, a member of the kinesin superfamily, is a microtubule-depolymerizing kinesin crucial for ciliary length control [2,4]. It localizes to cilia tips and its function is integral to the proper generation of fluid flow by cilia, which is essential for maintaining homeostasis in the mammalian body [2]. The AC6-AMPK pathway has been identified as an important regulator of Kif19a, where AC6 inhibits the degradation of Kif19a by suppressing autophagy [1].

Kif19a knockout (KO) mice display hydrocephalus and female infertility phenotypes due to abnormally elongated cilia that can't generate proper fluid flow, demonstrating the importance of Kif19a in ciliary length-related physiological functions [2]. In epithelium-specific knockout mice of AC6, airway epithelial cells have longer cilia because of decreased Kif19a protein levels in the cilia, suggesting that the AC6-AMPK pathway is a crucial ciliary growth checkpoint [1]. Additionally, in C. elegans, mutation in the depolymerizing kinesin-8 KLP-13/KIF19A suppresses the ciliary defects caused by a non-degradable nekl-4(PESTΔ) mutant, indicating its role in ciliary stability regulation [3,5].

In conclusion, Kif19a is essential for ciliary length control and proper fluid flow generation in mammals. The use of KO and conditional knockout (CKO) mouse models has been instrumental in revealing its role in cilia-associated disorders such as hydrocephalus and female infertility. Understanding the regulation of Kif19a through pathways like AC6-AMPK provides potential therapeutic targets for ciliopathies.