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Musical skill learning involves the integration of motor, perceptual, and cognitive processes and varies widely across individuals. While prior research has shown training-related brain plasticity, less is known about how baseline neural activity predicts learning success. We conducted a longitudinal study in music novices undergoing 6 weeks of piano training, including monozygotic twins and unrelated individuals to assess genetic contributions. Activity in the right hippocampus and amygdala during a melody learning task was positively associated with individual learning rates and pitch accuracies during the initial acquisition phase. This activity decreased with increasing melody length but remained stable across repetitions. Additionally, monozygotic twins showed greater similarity in pitch accuracy than unrelated individuals, suggesting a genetic influence on musical learning ability.