Rcn1, also known as reticulocalbin 1, is a calcium-binding protein located in the endoplasmic reticulum (ER) lumen. It contains six conserved regions and is involved in maintaining intracellular homeostasis, especially in regulating calcium homeostasis in the ER [1,2]. It also plays roles in regulating cell proliferation, apoptosis, and has been implicated in the unfolded protein response pathways [1,2,6]. Rcn1 is of great biological importance as it is involved in the development of various tumours and may also have a role in macrophage polarization [1,2].

Knockdown of Rcn1 in different cancer cell lines has shown significant effects. In oral squamous cell carcinoma (OSCC) and esophageal squamous cell carcinoma (ESCC), Rcn1 knockdown inhibited cell proliferation, migration, invasion, and EMT, and promoted apoptosis. It also inhibited M2 polarization of macrophages, suggesting its role in tumour microenvironment regulation [1,2]. In acute myeloid leukemia (AML), Rcn1 knockdown suppressed the viability of bone marrow mononuclear cells from AML patients and AML cell lines, and promoted pyroptosis through caspase-1 and gasdermin D (GSDMD) signaling. In the NSG mouse xenograft model, Rcn1 downregulation in human AML cells significantly inhibited tumour growth [3]. In non-small cell lung cancer (NSCLC), suppressing Rcn1 expression in A549 cells led to decreased cell proliferation, migration, and invasion [4]. In hepatocellular carcinoma (HCC), Rcn1 promotes tumour progression and sorafenib resistance, and its targeted therapy might be a feasible strategy [5].

In conclusion, Rcn1 is crucial for maintaining intracellular homeostasis, especially calcium-related functions. Through gene knockdown models in various cancer types, it has been shown to play a significant role in tumour progression, cell survival, and macrophage polarization. These findings suggest that Rcn1 could be a potential therapeutic target for cancers such as OSCC, ESCC, AML, NSCLC, and HCC.