This paper reviews the interrelationship between spermatogonial stem cells (SSCs) and the JAK/STAT signaling pathway, highlighting their roles in proliferation, maturation, and differentiation. SSCs, characterized by their self-renewal and pluripotential differentiation capabilities, are crucial for tissue regeneration and immunomodulation. The JAK/STAT pathway plays a pivotal role in modulating various functionalities of SSCs, including immunomodulation, tissue differentiation, homing, and adaptation to the microenvironment. The review discusses the historical background and biological characteristics of SSCs, emphasizing the importance of the JAK/STAT pathway in their processes. It also explores the implications of these interactions for preclinical research and cellular engineering. Despite advancements, human and large mammalian studies remain limited, necessitating further exploration to establish a comprehensive theoretical framework. The paper offers valuable insights into the mechanisms of SSC signaling pathways and their applications in regenerative medicine.This paper reviews the interrelationship between spermatogonial stem cells (SSCs) and the JAK/STAT signaling pathway, highlighting their roles in proliferation, maturation, and differentiation. SSCs, characterized by their self-renewal and pluripotential differentiation capabilities, are crucial for tissue regeneration and immunomodulation. The JAK/STAT pathway plays a pivotal role in modulating various functionalities of SSCs, including immunomodulation, tissue differentiation, homing, and adaptation to the microenvironment. The review discusses the historical background and biological characteristics of SSCs, emphasizing the importance of the JAK/STAT pathway in their processes. It also explores the implications of these interactions for preclinical research and cellular engineering. Despite advancements, human and large mammalian studies remain limited, necessitating further exploration to establish a comprehensive theoretical framework. The paper offers valuable insights into the mechanisms of SSC signaling pathways and their applications in regenerative medicine.