Wnk1, short for With No lysine (K) kinase 1, is a serine/threonine protein kinase. It participates in ion homeostasis via the WNK-OSR1/SPAK-NKCC cascade and is involved in various biological processes, including angiogenesis, cell migration, and metastasis [1,2]. Analyses of mouse models have been crucial in studying its functions [2,3].

In mouse models, Wnk1 has diverse effects. In vascular smooth muscle cells (VSMCs), deletion of L-Wnk1 leads to a pathogenic pro-inflammatory phenotype, causing aortitis and aortic wall remodeling [3]. In hepatocellular carcinoma (HCC) mouse models, liver-specific WNK1 knockout shows that WNK1 promotes HCC development by regulating ROS levels [4]. Myeloid-specific deletion of Wnk1 in mice results in a dramatic loss of tissue-resident macrophages (TRMs), disrupted organ development, and systemic neutrophilia [5]. Neuron-specific conditional KO (cKO) of Wnk1 in the brain causes polyuria with decreased urine osmolality and blunts arginine vasopressin (AVP) release in response to hyperosmolality [6].

In conclusion, Wnk1 is essential in multiple biological processes. Mouse models, especially KO and CKO models, have revealed its roles in diseases such as aortitis, HCC, and those related to macrophage development and water homeostasis regulation. Understanding Wnk1's functions provides insights into disease mechanisms and potential therapeutic targets.