This study investigates the essential role of Plzf (Zfp145) in the maintenance and self-renewal of spermatogonial stem cells. Plzf is a transcriptional repressor expressed specifically in gonocytes and undifferentiated spermatogonia, which are the mitotic germ cells of the testis. Mice lacking Plzf exhibit a progressive loss of spermatogonia with age, characterized by increased apoptosis and subsequent loss of tubule structure. Spermatogonial transplantation experiments revealed a depletion of spermatogonial stem cells in adult mice. Microarray analysis of spermatogonia from Plzf-deficient mice showed alterations in the expression profile of genes associated with spermatogenesis. These findings identify Plzf as a critical transcription factor in the testis that is essential for regulating the self-renewal and maintenance of the stem cell pool in spermatogonia.This study investigates the essential role of Plzf (Zfp145) in the maintenance and self-renewal of spermatogonial stem cells. Plzf is a transcriptional repressor expressed specifically in gonocytes and undifferentiated spermatogonia, which are the mitotic germ cells of the testis. Mice lacking Plzf exhibit a progressive loss of spermatogonia with age, characterized by increased apoptosis and subsequent loss of tubule structure. Spermatogonial transplantation experiments revealed a depletion of spermatogonial stem cells in adult mice. Microarray analysis of spermatogonia from Plzf-deficient mice showed alterations in the expression profile of genes associated with spermatogenesis. These findings identify Plzf as a critical transcription factor in the testis that is essential for regulating the self-renewal and maintenance of the stem cell pool in spermatogonia.