Relative abundance of proteins localised in the nuclear-enriched, total cell membrane and cytosolic fractions of the semitendinosus muscle was compared between lambs bred from control (C), high muscling (M), and high growth rate (G) sires. In total, 31 proteins were identified whose abundance was differentially regulated between sire type. Differences in hind-limb muscle development between M lambs and C and G lambs were reflected in levels of proteins that regulate or function in cellular mechanisms of protein and energy metabolism. Despite no apparent difference in hind-limb muscle growth in G lambs compared to C, G lambs exhibited marked differences in proteins involved in regulation and function of energy metabolism. These results detail pathways that can be specifically targeted to enhance muscle accretion and growth in lambs. The development of means to manipulate these cellular mechanisms may yield greater gains in muscle accretion and growth rate than breeding on the basis for genetic capacity alone.