Hspa2, a member of the HSPA (HSP70) family, was initially thought to be testis-specific and is crucial for male fertility. It plays important roles in germ cell development during spermatogenesis, such as facilitating the progression of germ cell differentiation in mice [3,4]. It also has functions in sperm functional transformation, like coordinating the remodelling of sperm domains for oocyte recognition [3].

In diabetes-related heart failure, higher Hspa2 expression in the myocardium and its corresponding higher plasma protein concentration are associated with impaired left ventricular (LV) contractility, increased LV mass, incident heart failure, and cardiovascular mortality [1]. In pancreatic cancer, upregulated Hspa2 independently predicts early postsurgical recurrence and has superior predictive performance when combined with malignant clinicopathologic features [2]. In addition, Hspa2 may serve as a biomarker for human sperm in vitro capacitation, spermatogenesis status, and potentially for complementing classic seminal analysis before assisted reproduction techniques [5,6,7].

In conclusion, Hspa2 is essential for male reproductive processes. Its dysregulation is also associated with diabetes-related heart failure and pancreatic cancer recurrence. Research on Hspa2 using mouse models has provided insights into its role in these biological processes and disease conditions, potentially guiding future therapeutic strategies and biomarker-based diagnosis.