NCF2, also known as neutrophil cytosolic factor 2, encodes the cytosolic factor p67phox. It is a crucial component of the NADPH oxidase complex, which generates reactive oxygen species (ROS) in phagocytes, playing a vital role in the immune system's defense against pathogens [1,6]. The NADPH oxidase pathway, in which NCF2 is involved, is essential for innate immunity [1,6].

Mutations in NCF2 result in autosomal recessive chronic granulomatous disease (CGD), a rare primary immunodeficiency disorder [1,6]. For instance, a novel c.855G>C NCF2 mutation led to diverse clinical phenotypes in patients, including suspected early onset interstitial lung disease, severe pneumonia, lymphadenitis, and recurrent skin abscesses [1]. Another study reported a homozygous variant in NCF2 (c.290C > A) that caused severe disseminated BCG infectious disease in a patient [6]. In hepatocellular carcinoma, higher NCF2 expression predicted an adverse prognosis and more M2 macrophages infiltration [2]. Also, NCF2 was identified as a diagnostic gene of atherosclerosis and may be involved in the formation of the necrotic core by regulating macrophage ferroptosis [3]. In bladder cancer, lncRNA BLACAT3 enhances NCF2 transcription to promote angiogenesis and hematogenous metastasis [4]. Moreover, in cyclophosphamide-induced alopecia, S100A8 promotes ferroptosis via the NCF2/NOX2 pathway [5]. In pan-cancer analysis, NCF2 is dysregulated in many cancers, is an independent prognostic factor for leukemia, and impacts the tumor microenvironment and therapeutic responses [7]. Additionally, NCF2, along with three other genes, may be potential noninvasive diagnostic biomarkers for obstructive coronary artery disease [8].

In conclusion, NCF2 is essential for the proper function of the NADPH oxidase complex and innate immunity. Studies of NCF2 mutations in patients have revealed its significant roles in various diseases, including primary immunodeficiency disorders, cancers, atherosclerosis, and chemotherapy-induced alopecia. Understanding the function of NCF2 provides insights into the underlying mechanisms of these diseases, which may potentially lead to new diagnostic and therapeutic strategies.