Germ cell tumors (GCTs) account for 3% of malignancies in children under 15 years of age and almost 14% of malignancies in 15–19-year-old adolescents. Although chemotherapy is effective in most patients, it causes significant acute and long-term toxicities, and a subset of patients develop therapy-refractory or relapsed disease against which current treatments are ineffective. Thus, there is a strong need to better understand the risk factors for GCTs to counter the rising incidence of these cancers affecting pediatric, adolescent and young adult populations. Major GCT risk factors include genetics, developmental abnormalities, and environmental exposures. How these risk factors impact GCT incidence is a key knowledge gap that has persisted in part due to a lack of accurate experimental models. We previously generated a mouse testicular GCT (TGCT) model known as germ cell-specific Pten and Kras mutant (gPAK) mice, which develop metastatic mixed germ cell tumors that closely resemble human TGCTs. gPAK TGCTs, like those in humans, originate during embryonic germ cell development, creating a powerful new model to elucidate mechanisms in TGCT initiation and test the influences of candidate risk factors. We hypothesize that developmental and genetic risk factors for TGCTs promote tumor initiation by extending the period when PGCs exist in a transformation-susceptible state. We will test this hypothesis by combining the gPAK model with genetic (Aim 1) and developmental (Aim 2) manipulations associated with TGCT risk in humans. while also elucidating the underlying mechanisms through both a candidate-based approach focused on pluripotency, proliferation, and cell death, and unbiased discovery using single cell RNA sequencing.