Molten Shrine - Skullmaw Stairway

Reward: +5% Increased Maximum Life
How to Get: Pick up and Path of Exile 2 Currency activate the Molten One's Gift.
Reversible: No.

A must-grab for tankier builds, this scales with all life modifiers later in the game.

Akhti and Anundr - The Khari Crossing

Reward: +2 Weapon Set Skill Points
How to Get: Trigger the "Clearing the Way" quest from Risu in The Khari Bazaar, then defeat the bosses.
Reversible: No.

Another reliable way to expand your weapon set customization.

Interlude 3: Kriar Village and Howling Caves

Lythara, the Wayward Spear - Kriar Village

Reward: +40 to Spirit
Reversible: No.

This permanent boost is massive for Spirit-based builds, providing both resource scaling and synergy with buy POE 2 Chaos Orbs certain skill mechanics.

The Abominable Yeti - Howling Caves

Reward: +2 Weapon Set Skill Points
Reversible: No.

Completing this fight nets yet another important weapon skill point boost.