According to the Human Protein Atlas, there are 19,613 proteins encoded by the human genome. Of these, 14,545 (74%) have no known link or relationship with disease, which rules them out as potential new drug targets because they fail to meet criterion 1 above. Perhaps these proteins are non-essential, as any deficiencies can be compensated by other proteins or pathways; or perhaps they are essential, however any deficiencies are lethal before birth so they never have the chance to cause any disease. In any case, we have no reason to believe that targeting these proteins will do anything for any known human disease. Now of the 5,068 proteins that have any link to disease, 3,131 (16% of all human proteins) are considered to be “undruggable”, either because they have no obvious pocket capable of binding small molecule drugs, or because they are intracellular and thus inaccessible to large proteins that cannot penetrate the cell membrane. We must rule out these proteins as potential new drug targets because we currently have no way to target them, so they fail to meet criterion 2 above. - https://endpts.com/pharmas-broken-business-model-part-2-scraping-the-barrel-in-drug-discovery/