Pde4c, a member of the Phosphodiesterase type 4 (PDE4) enzyme family, specifically hydrolyses cAMP in numerous cell signalling systems transduced by hormones and other primary messengers [1]. It is involved in cAMP catabolic process, and in thyroid carcinoma (THCA), it participates in cAMP metabolic process by regulating adenylate cyclases (ADCYs) [2].

In THCA, the expression level of PDE4C is significantly up-regulated, and patients with higher PDE4C expression have shorter progress-free survival, suggesting it could be a potential prognostic marker [2]. In osteosarcoma, PDE4C derived from M2 macrophages increases cell proliferation and mobility via upregulating collagen expression, and is associated with prognosis and immunotherapy response [3]. In adenomyosis, TCF21 upregulation impairs endometrial decidualization by increasing PDE4C expression, which in turn inhibits intracellular cAMP levels [4]. In glioma, PDE4C may function as a tumor suppressor as its down-regulation through promoter hypermethylation is associated with grade progression and overall survival [5]. In French bulldogs, a heterozygous variant in PDE4C is associated with muscle hypertrophy, dysphagia, and gait abnormalities [6].

In conclusion, Pde4c is crucial in cAMP-related signalling pathways. Studies in various disease models such as THCA, osteosarcoma, adenomyosis, glioma, and in a canine model, have shown its diverse roles in disease progression, prognosis, and cellular functions, highlighting its potential as a therapeutic target and biomarker.