CaMK4, also known as calcium/calmodulin-dependent protein kinase IV, is a versatile serine/threonine kinase. It is involved in a wide range of cellular functions, regulating pathways related to T-cell differentiation, podocyte function, tumor cell proliferation/apoptosis, β-cell mass, and insulin sensitivity. Genetic models, such as gene knockout (KO) mouse models, have been crucial in understanding its functions [1].

In KO mouse models, CaMK4-deficient T cells led to impaired germinal center formation and humoral immunity in immunized mice, and reduced anti-dsDNA titres, as well as IgG and complement kidney deposition in lupus-prone B6.lpr mice, indicating its role in T-follicular helper (Tfh) cell-mediated autoimmunity [2]. In psoriasis, Camk4-deficient mice treated with imiquimod (IMQ) had reduced psoriasis severity, with changes in macrophage and IL-17A+γδ TCR+ cell numbers, showing its role in psoriatic inflammation [3]. In acute lung injury (ALI), inhibition of CaMK4 in type II alveolar epithelial cells (AEC II) significantly inhibited NLRP3 inflammasome activation and reduced IL-1β production, ameliorating lung injury in LPS-induced ALI mice [4]. In osteoarthritis (OA), CaMK4 expression increased in the knee joint synovial tissue of mice after destabilization of the medial meniscus (DMM), and cartilage damage improved after intraperitoneal administration of the CaMK4 inhibitor KN-93 [5].

In conclusion, CaMK4 is essential in regulating multiple biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significant contributions to diseases such as autoimmunity, psoriasis, ALI, and OA. Understanding CaMK4 functions provides potential therapeutic targets for these diseases.