Ana Sarinho, Maria Eugénia Marques Da Costa, Janaina Lima, Leonardo Batista, Rogério Andrade, Jéssica Gonçalves, Carolina Silva, Hugo M. Lisboa
• Chemistry-forward review of press-cake and hull valorization from pumpkin seeds. • Benchmarks extraction routes by yield, purity, selectivity, scalability, E-factor. • Maps protein/peptide structure to solubility, emulsifying, foaming and gelling. • Links functionality to product performance in bakery, meat, and dairy-alternatives. • Outlines zero-waste biorefinery integrating SC-CO₂, DES/subcritical, aqueous steps. Agrifood side streams from pumpkin processing—seed press-cake and seed hulls—provide underexploited sources of proteins, fibers, lipophiles, and phenolics. This review links green-extraction chemistry to structure–function behavior of pumpkin seed proteins. We evaluate extraction and modification routes by how well they serve food end-uses, grading evidence across yield, purity, digestibility, and interfacial/gel performance. We show that aligning process sequence with function—oil polishing and phenolic tuning before protein isolation, then moderate structure modification—outperforms one-step approaches for neutral-pH beverages, while alkali ± intensification suffices for savory bakery/meat systems. We map molecular determinants to solubility, interfacial activity—emulsifying activity index (EAI) and emulsion stability (ES)—foaming, and gelation, and how phenolics and antinutrients modulate functionality, digestibility, and bioaccessibility. A matrix benchmarks supercritical carbon dioxide (SC-CO₂), deep eutectic solvents (DES), subcritical ethanol–water, pH-shift/isoelectric precipitation, enzyme-assisted routes, and physical intensification for selectivity, scalability, and eco-metrics. Moderate ultrasound or heat-assisted pH-shifting increases solubility and emulsification; mild thermal/alkaline regimes reduce phytic acid and trypsin inhibitors and raise in-vitro protein digestibility (≈86→96%); protein–polysaccharide hybrids enhance oxidative stability. We outline a zero-waste biorefinery sequencing SC-CO₂ for oil; DES or subcritical ethanol–water for phenolics; and aqueous/enzymatic steps for proteins/peptides with solvent recycling. We conclude with priorities for standardization, bioavailability, scale-up, and clean-label formulation.