Runes do not appear in Diablo 4 despite being teased early in development. This page details what has been teased, mentioned, and datamined from game files.
Runes appeared in a limited capacity in Diablo 1 but it was not until Diablo 2 that an entire system was built around runes in the form of [Runewords]. Runes were collected as loot and socketed in a particular order in Grey items. Combinations of runes formed Runewords and applied bonuses to the item they were socketed into. It proved very popular and was much requested in Diablo 4.
Early in development, Blizzard teased the notion of a reworked system using Runes appearing in the game. Runes would be socketed in pairs with a 'Condition Rune' and a 'Effect Rune'. The Condition would be the activation rune, which action triggers the second rune's power such as 'When you are stunned...' or 'When your pet dies...'. The Effect Rune would be what happens when triggered, for example, 'Gains a random shrine effect' or 'Reduce a random skill's cooldown by 15%'.
Over time, runewords were removed from the game but it's worth noting that they may still return. In an interview on Wccftech in April 2023, Lead Class Designer Adam Jackson added:
Yeah, totally. How would I say this? We like rune words. They're very cool. We don't have anything to announce as far as if they're going to be in the game in the immediate future. We do think they're still a really cool idea, and that's all I'm going to say right now.
Some of the Diablo 4 runes were confirmed when they first appeared but the socketed properties in Diablo 4 were different from the properties in Diablo 2. Below is a list of all the runes players expected to see based on the Diablo 2 runes. The list shows runes that were confirmed for Diablo 4 and their new properties.