Proteins denature when subjected to extreme conditions such as high temperatures or altered pH levels, which disrupt the electrostatic and hydrogen bonds that maintain their folded structure. Denaturation is essentially the unfolding of proteins, driven by the thermodynamics of the folded versus unfolded states. Increased pressure and temperature provide enough energy to break these bonds, while changes in pH can affect the electrostatic interactions between peptides, altering the protein's energy state. Cold denaturation is a complex process where proteins lose energy to their environment, leading to unfolding. Chemical denaturation involves breaking disulfide bridges and can result in protein degradation. Detergents can also induce denaturation by interacting with hydrophobic regions of proteins. Despite advancements in understanding protein folding and denaturation, many aspects remain enigmatic. Additionally, high internal body temperatures can lead to permanent denaturation of proteins in critical areas like the hypothalamus, significantly impacting physiological functions and survival rates in cases of heat stroke.