HSPH1, also known as heat shock 105kDa/110kDa protein 1, is a member of the heat shock protein family. Heat shock proteins play crucial roles in maintaining protein homeostasis, such as preventing protein aggregation, assisting in protein folding, and participating in stress response pathways [5,8].

In cancer research, HSPH1 has been implicated in multiple types of cancers. In gastric cancer, it was identified as a target of ATF2. HSPH1 can interact with SLC7A11 to increase its protein stability, and knockdown of HSPH1 partly reversed the inhibitory effect of ATF2 overexpression on sorafenib-induced ferroptosis [1]. In advanced lung adenocarcinoma, the rs2280059 genetic variant of HSPH1 modulated its expression, and silencing HSPH1 significantly increased the antineoplastic effects of gefitinib [2]. In aggressive B-cell non-Hodgkin lymphoma, HSPH1 silencing downregulated Bcl-6 and c-Myc, hampering the growth of lymphoma cells both in vitro and in vivo [6]. In prostate cancer, HSPH1 may promote the differentiation of conventional T cells towards Th1 or Th2 cells, increase CD8 + T cells in the tumor area, and inhibit prostate cancer invasion [3]. In addition, in N-methyl-N-nitrosourea-induced gastric carcinogenesis, YTHDF1 regulated the translation of HSPH1, affecting malignant transformation and tumorigenesis [4].

In acute lung injury, the IL-1β/KLF2/HSPH1 pathway was activated, facilitating STAT3 phosphorylation in alveolar macrophages and exacerbating pulmonary inflammation [7]. Also, HSPH1 was found as a potential biomarker in doxorubicin-induced chronic cardiotoxicity [9].

In conclusion, HSPH1 is an important gene involved in protein-related cellular functions and stress responses. Its dysregulation is associated with various diseases, especially cancers. Studies using gene-knockdown or other loss-of-function models have revealed its roles in promoting cancer cell growth, drug resistance, and influencing disease-related signaling pathways, providing potential therapeutic targets for these diseases.