AHNAK, also known as desmoyokin, is a large, ubiquitously expressed scaffolding phosphoprotein with a size of approximately 700 kDa. It plays a crucial role in mediating protein-protein interactions, enabling its participation in various multi-protein complexes. This leads to its involvement in diverse biological processes such as tumour suppression, immune regulation, cell architecture maintenance, and calcium homeostasis [1,2]. In calcium homeostasis, it mainly interacts with the L-type voltage-gated calcium channel (LVGCC) in excitable cells [1].

In ovarian cancer, overexpressing AHNAK represses cell growth and metastasis, suppressing cancer progression via the Wnt/β-catenin signaling pathway [4]. In nasopharyngeal carcinoma, silencing AHNAK promotes cancer progression by upregulating the ANXA2 protein [6]. In hepatocellular carcinoma, AHNAK contributes to cancer growth by interacting with IGF-1R [5]. In primary localized cutaneous amyloidosis, OSMR mutations lead to elevated AHNAK expression, causing hyperproliferation and overdifferentiation of keratinocytes [3]. Ahnak knockout (KO) mice studies show that Ahnak enhances TGF-β signaling during postoperative liver regeneration, disrupting the cell cycle [7].

In conclusion, AHNAK is a multifunctional protein involved in various biological processes and diseases. Studies using gene knockout models, especially in cancer and skin disease research, have revealed its role in regulating cell growth, metastasis, and differentiation. These findings provide potential biomarker and treatment target insights for related diseases.