Poor Lonnie gets a pretty bad rap in this book from a lot of people. Lily calls him "hopeless" (1.5), Pop says he's a "loony" (5.42), and Marigold describes him as "fragile" (12.22). And in a way, they've got a right to say all this—after all, changing college majors and career choices multiple times doesn't exactly present a picture of stability.
In Lonnie's defense, though, not all students head into college knowing exactly what they want to do with their lives; for many, it takes a period of exploration and self-discovery to truly find their callings. It makes sense that this would be the case for Lonnie, since he's always been kind of unfocused—Lily even states that she's always felt like a mother figure to him while "He was like a toddler" (2.11) and "some frail and helpless creature" (2.25). So what did they all think was going to happen when Lonnie went to school? Seems like Lonnie's just being Lonnie, after all.
In his mind, Lonnie links his drifting sense of purpose with the absence of his father, which probably accounts for some of the identity issues he experiences:
Now the familiar panic began to surge inside him, the panic that had sent him to the Admin buildings of two colleges to give up his course […] he'd felt at home with English Lit, but this feeling must also have been an illusion, like having a dad had been an illusion. (9.5)
It's hard to say for sure, but being abandoned by his dad couldn't have done much for his self-image. From the sounds of it, when Lonnie starts to get comfortable, he freaks out. Which given how comfortable he must've felt with his dad, makes sense—dude just bounced one day. No wonder Lonnie doesn't trust feeling at home.
In spite of everything stacked against him, though, Lonnie undergoes a major transformation throughout the course of the story. He doesn't quit English Lit, he develops a relationship with Clara based on their mutual ostracism at home, and most importantly, he gains a sense of purpose and maturity by realizing that he wants to marry her:
He could sense an invisible audience of people whose mouths would drop open if he so much as whispered such intentions, who would exclaim: "You?" as if he was twelve instead of twenty-two. (30.24)
Lonnie knows people might be shocked or disapprove of his intentions with Clara, but he doesn't care. He's confident he's doing the right thing for himself, which, to return to the whole discomfort-with-feeling-at-home idea, seems like a giant step in the right direction for Lily's older brother.