Ulk2, also known as unc-51 like autophagy activating kinase 2, is a key kinase in the autophagy pathway, with functions similar to its yeast homolog Atg1 [2,3,6]. Autophagy is a lysosome-dependent degradation pathway crucial for maintaining cellular homeostasis, and Ulk2 has been implicated in regulating this process, along with its potential roles in other cellular signaling pathways [2,3]. Genetic models, such as gene knockout mouse models, are valuable tools for studying Ulk2's functions.

In skeletal muscle, ULK2-deficient adult mice show accumulations of insoluble ubiquitinated protein aggregates associated with SQSTM1 and NBR1, leading to impaired muscle force, myofiber atrophy, and degeneration, indicating its unique role in basal selective protein degradation [4]. In ovarian cancer, ULK2 is significantly downregulated, and its overexpression suppresses tumor cell proliferation, migration, and invasion, suggesting it acts as a tumor suppressor by upregulating IGFBP3 [1]. In gastric cancer, methylation-mediated silencing of ULK2 can induce cell migration and epithelial-mesenchymal transition (EMT) through autophagy induction, causing transformation to poorly differentiated cancers [5].

In conclusion, Ulk2 is essential for maintaining protein homeostasis in skeletal muscle and has significant implications in cancer development. The use of KO/CKO mouse models has revealed its role in regulating basal protein degradation in muscle and its potential as a tumor suppressor in ovarian and gastric cancers, providing valuable insights into disease mechanisms and potential therapeutic targets.