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Although human milk has been studied for decades, big strides have been made in very recent years, owing to the introduction of innovative qualitative and quantitative approaches in proteomics. Since our recent report on the human milk proteome, where 285 unique proteins were listed, almost two years of research in this field have generated an updated inventory consisting of 761 entries. This huge increment might further boost improvements in the field of novel nutritional formulas. By performining bioinformatic analysis on this updated dataset, we here substantiate that, despite the significant increase in the overall entries, human milk proteins are mainly devoted to three main biological functions, which include nutrient transport/lipid metabolism, concretization of the immune system response and mediation of cellular proliferation processes. Of note, human milk proteins seem also to promote maturing of the immune and central nervous system, through a series of biological mediators, including hormones, cytokines and other signaling molecules. Furthermore, the introduction of novel technological approaches has also helped furthering our understanding of the quantitative fluctuations of human milk proteins; this issue may represent a key aspect in the design of novel infant formulas as much as close to the actual breast milk.