Serpinb3a, also related to squamous cell carcinoma antigen (SCCA), is a serine-protease inhibitor. It is involved in multiple signal transduction pathways, including the lysosomal necrosis cell death pathway which overlaps with radiation-induced apoptosis [2]. It also plays a role in the regulation of protease activities, as it can inhibit both serine and cysteine proteinases [5,6].

In gene knockout (KO) mouse models, Serpinb3a-/-mice showed radioresistance compared to Serpinb3a + / + mice, with long-term bone marrow cultures from Serpinb3a-/-mice having increased longevity [2]. In asthma models, Serpinb3a-null mice had attenuated airway hyperresponsiveness and goblet cell hyperplasia, revealing its role in mucus production through regulation of SPDEF expression [3]. In atopic dermatitis models, Serpinb3a-null mice had attenuated barrier dysfunction and early inflammatory response following cutaneous allergen exposure [4]. In cancer, intratumoral knockdown of Serpinb3a in mouse models led to tumor growth inhibition, reduced myeloid cell infiltration, enhanced cytotoxic T-cell function, and sensitized tumors to radiotherapy [1].

In conclusion, Serpinb3a KO mouse models have revealed its significant roles in radiation response, asthma-related mucus production, atopic dermatitis-associated barrier function and inflammation, as well as in tumor immunity and response to radiotherapy. These findings highlight the importance of Serpinb3a in understanding the mechanisms of these diseases and potentially developing new therapeutic strategies.