A day we expected to come but now Riot Games have formally announced that their Vanguard kernel-level anti-cheat is coming to League of Legends, and so it will make it unplayable on Linux. This is the same tech they use in VALORANT, which is also unplayable on Linux due to it.
This news was confirmed in their recent developer video below at about 12:43, mentioning it will happen in either late February or early March:
Speaking on Reddit, one of their team mentioned "We'll get some more info about Linux for you all soon, it's not something i know the answer to off the top of my head and I want to make sure I talk with the team and get you the right info.", and in a previous comment they mentioned Vanguard won't be used in the macOS version.
However, a different Riot staff member seemed to make it clear Linux support won't be happening in reply to a user asking about playing it in Wine: "No unfortunately not. From a security point of view supporting WINE would be like having a bank vault at the top of Nakatomi Tower then installing a doggy door in it.".
Considering that to play it on Linux you need to run the Windows version through Wine, there's no way they're going to roll out Vanguard into the Windows client and just let Linux get off without it. So I fully expect it to become unplayable in the next couple of months.
Seems like it's time for League of Legends players on Linux to finally swap over to Valve's Dota 2, which has full Native Linux support.