The emerging role of CAMK1D in diabetes, metabolism and feeding behaviours: A mechanistic systematic review

Background: Diabetes, metabolic disorders and feeding behaviours continue to pose significant public health challenges. Calcium/calmodulin-dependent protein kinase ID (CAMK1D) has recently emerged as a pivotal molecule potentially bridging peripheral metabolic control with central appetite regulation. Therefore, a comprehensive review was performed to critically evaluate and synthesize current evidence regarding the role of CAMK1D in diabetes, metabolic processes and feeding behaviours. Main text: The review assessed both published results (263 non-duplicate studies; across Pubmed, WebOfScience and EMBASE) and the grey literature (including 14 patents, 3 clinical trials). Results from 43 unique studies, 2 patents and 5 genome-wide association studies were finally summarized. CAMK1D modulates both metabolic processes and feeding behaviours, exhibiting tissue-specific dynamics and diverging regulatory control either in the central nervous system (i.e., hypothalamic nuclei regulating appetite and satiety) or in the periphery (i.e., pancreatic beta cells). Genetic studies highlighted significant associations between CAMK1D polymorphisms and increased susceptibility to diabetes, obesity and altered feeding behaviours. Conclusions: CAMK1D represents an emerging molecular target with promising implications for the treatment of a wide range of clinical conditions. However, further large-scale, mechanistic and longitudinal studies are warranted to validate its role across physiological and pathophysiological conditions, as well as to explore its future therapeutic potential.