Plcd1, or Phospholipase C delta 1, encodes an enzyme involved in regulatory signaling of energy metabolism, calcium homeostasis, and intracellular movement [4]. It is essential for epidermal barrier integrity and plays a role in intracellular signal transduction [6].

Mutations in Plcd1 have been linked to various diseases. In families with multiple trichilemmal cysts, predisposing variants in PLCD1 were identified, suggesting a monoallelic mutational mechanism for cyst formation [1]. A germline missense variant of PLCD1 was found in a Chinese family with autosomal dominant multiple pilomatricomas. This variant increased the enzymatic activity of PLCδ1, leading to activation of the protein kinase C/protein kinase D/extracellular signal-regulated kinase1/2 pathway and TPRV6 channel closure, resulting in excessive keratinocyte proliferation and calcium accumulation in the tumors [6]. In addition, in chondrosarcoma, lower PLCD1 expression was detected mainly in high-grade tumors, and overexpressing PLCD1 induced DNA damage, causing cell cycle blocking and apoptosis [2]. In esophageal squamous cell carcinoma (ESCC), PLCD1 expression was downregulated, and upregulation of PLCD1 decreased the capacity of TE-1 and EC18 cells in proliferation, invasion, and migration, potentially through inhibition of the Wnt/β-catenin signaling pathway [3]. In breast cancer, PLCD1 was frequently downregulated/silenced by promoter methylation, and its ectopic expression inhibited colony formation, cell migration, and induced cell cycle G(2)/M arrest [4]. In colon cancer, miR-17-3p facilitated cancer cell progression by downregulating PLCD1 [5]. In oral squamous cell carcinoma, miR-191 regulated cell growth by targeting PLCD1 via the Wnt/β-catenin signaling pathway [7].

In conclusion, Plcd1 is involved in multiple biological processes and is associated with various diseases, including skin cysts, skin tumors, and several types of carcinomas. Studies on Plcd1, especially those using genetic models, have enhanced our understanding of its role in disease-related biological processes, potentially providing new therapeutic targets for these diseases.