Ryan McNess, Umar Shah, Hani Al-Salami, Sarita Jane Bennett, Stuart Johnson, Rewati Raman Bhattarai
: Lupins are high-protein, high-fibre grain legumes, gaining global popularity as plant-based human food with potential health benefits. Cellular, animal model, and a single human study on one protein component of lupin seed, γ-conglutin, have demonstrated its blood glucose-modulating effects, with potential value for the prevention of type 2 diabetes (T2D). However, the commercial production of a γ-conglutin supplement or nutraceutical and its application in blood glucose management are currently hindered by significant technological barriers to extraction and purification, and analytical barriers to quantification. Current methodologies for purifying γ-conglutin from lupin seeds are ineffective; γ-conglutin purity in enriched fractions is typically lower due to other proteins, salts, and sugars. High alkaline pH promotes partial denaturation and oxidation of sulphur-containing amino acids, thereby altering disulphide-linked structures and leading to loss of structural features and, eventually, loss of structure-associated bioactivity. Other reported methods (salt-assisted precipitation, membrane separation, and chromatographic purification) remain limited by low yields, purity, and scalability. Current LC–MS approaches have improved the specificity and sensitivity of γ-conglutin quantification compared to early ELISA-based methods; however, challenges remain, including incomplete protein extraction from complex matrices and limited simultaneous identification and quantification of conglutin fractions. Research is required to develop high-purity, scalable extraction and purification processes, along with high-accuracy, specific, and sensitive analytical methods, for quantifying γ-conglutin peptides throughout processing. This review attempts to bring together extraction, purification, quantification, digestion, bioavailability, and future nutraceutical applications of γ-conglutin.