Cdkn2c, also known as Cyclin-Dependent Kinase Inhibitor 2C or p18INK4C, is a cell growth regulator. It controls cell cycle progression and is involved in multiple biological pathways such as insulin signaling, fatty acid and carbohydrate metabolism [1]. It has been associated with an increased risk of type II diabetes (T2D) and reduced peripheral adipose tissue storage capacity [1].

In T2D and obese subjects, the expression of Cdkn2c in subcutaneous and omental adipose tissue is reduced compared to controls [1]. Knockdown of Cdkn2c in human preadipocytes led to lower expression of differentiation markers and transiently reduced lipid accumulation per adipocyte during differentiation, suggesting its role in adipose lipid storage [1].

In medullary thyroid carcinoma, the presence of Cdkn2c loss was associated with worse M stage, overall AJCC stage and decreased overall survival, especially when combined with RETM918T mutation [2]. In melanoma, miR-21-5p promotes cell proliferation and G1/S transition by targeting Cdkn2c, indicating its role in cell cycle regulation in melanoma [3]. In gastric cancer, c-Myc and PRMT5 interact to transcriptionally repress Cdkn2c expression, promoting gastric cancer cell growth [4]. In esophageal squamous cell carcinoma, LINC00673 represses Cdkn2c expression and promotes cell proliferation by EZH2-mediated H3K27 trimethylation [5]. In lung adenocarcinoma, CBX8 promotes growth and metastasis through transcriptional repression of Cdkn2c [6].

In conclusion, Cdkn2c plays a crucial role in regulating cell cycle progression, adipose lipid storage, and is involved in the development and progression of multiple diseases including type II diabetes, medullary thyroid carcinoma, melanoma, gastric cancer, esophageal squamous cell carcinoma, and lung adenocarcinoma. Functional studies such as gene knockdown in relevant cell models have been instrumental in revealing its roles in these biological processes and disease conditions.