Popdc3, a transmembrane protein, contains a unique cyclic adenosine monophosphate (cAMP) binding site. It is widely expressed in mammalian tissues, with the highest levels in skeletal muscle. POPDC3 is involved in cAMP signaling and plays a key role in many physiological and pathological processes. It is considered a candidate biomarker and potential therapeutic target for cancer. Additionally, its gene variants have been associated with limb-girdle muscular dystrophy (LGMD) type 26 [1,2,3,6].

Functional analyses in zebrafish popdc3 knockdown models showed that knockdown of popdc3 resulted in larvae with tail curling and dystrophic muscle features, indicating its importance for skeletal muscle function [2]. In Xenopus laevis oocytes, mutant POPDC3 proteins caused aberrant modulation of the mechano-gated potassium channel, TREK-1 [2]. In head and neck squamous cell carcinoma (HNSCC), high POPDC3 expression correlated with poor prognosis and radioresistance [4]. In gastric cancer, reduced Popdc3 expression was associated with depth of invasion, lymph node metastasis, and poor survival [5].

In conclusion, POPDC3 is crucial for skeletal muscle function and is implicated in cancer-related processes such as prognosis and radioresistance in HNSCC, as well as carcinogenesis and progression in gastric cancer. The use of knockdown models in zebrafish and functional studies in Xenopus oocytes have revealed its role in muscle function and ion channel modulation. These findings highlight the significance of POPDC3 in both normal biological functions and disease conditions [1,2,4,5].