Some of the factors that affect protein solubility in a given formulation include pH, ionic strength and solids content. In general, proteins are least soluble at their isoelectric point. The isoelectric point of lactalbumin proteins ranges from 4.2 to 4.5 and of lactoglobulin from 5.3 to 5.5.

As a general rule, proteins that are undenatured are most soluble. Heating whey proteins results in protein denaturation, decreasing solubility. Various polyols and sugars can stabilize proteins against heat denaturation. Generally, as the water content of a solution decreases, the amount of heat required to denature protein increases.